The molecular crowding of the cytoplasm impacts a range of cellular processes. Using a fluorescent microrheological probe (GEMs), we observed a striking decrease in molecular crowding during the yeast to filamentous growth transition in the human fungal pathogen Candida albicans. This decrease in crowding is due to a decrease in ribosome concentration that results in part from an inhibition of ribosome biogenesis, combined with an increase in cytoplasmic volume; leading to a dilution of the major cytoplasmic crowder. Moreover, our results suggest that inhibition of ribosome biogenesis is a trigger for C. albicans morphogenesis. The cytoplasm is a crowded environment and molecular crowding can affect a range of biological functions 1,2 , including chemical reaction rates, protein complex formation and rates of cytoskeletal protein polymerization 3-5 . In the budding yeast Saccharomyces cerevisiae and mammalian cells the target of rapamycin complex (TORC) was shown to regulate ribosome concentration, and inhibition of TORC1 resulted in increased cytoplasmic fluidity 6 . More recently, cell cycle arrest mutants were shown to result in decreased macromolecular crowding of the cytoplasm, in part via ribosome downregulation 7 . Little is known about the relationship between molecular crowding in the cytoplasm and morphological growth states, for example when the human fungal pathogen Candida albicans switches from an ovoid yeast form to a filamentous hyphal form, a transition essential for virulence. Here, we show that there is a dramatic decrease in molecular crowding during filamentous growth, which is mediated by inhibition of ribosome biogenesis and subsequent dilution of this critical cytoplasmic crowder as a result of new growth. We propose that ribosome levels are tuned to regulate crowding in distinct growth states in this fungal pathogen. Furthermore, our results highlight that despite the new growth that occurs during the yeast-to hyphal transition, there is a substantial decrease in ribosome levels. To investigate the link between cytoplasmic diffusivity at the mesoscale and cell morphology we took advantage of passive microrheological probes 6 , for which we can measure dynamics both in budding and hyphal cells. We used C. albicans cells expressing 40-nm GEMs. We imaged every 30 msec to obtain a signal sufficient for single particle tracking. The mean track length was 10 frames, which corresponds to 300 msec of imaging. The effective diffusion coefficient, Deff, which is inversely proportional to microviscosity for Brownian motion, was determined from the first 120 msec of acquisition. Temporal projections that were false colored for GEM distribution in budding cells, fixed budding cells and cells treated with fetal bovine serum for 60 min, in which a filament is evident, are shown in Figure 1A, with trajectories of GEMs in representative budding and filamentous cells. Fixation