Trichomonas vaginalis, grown in Dulbecco's modified Eagle's medium with or without serum, produced a factor (TVF) which altered the morphology of certain mammalian cells in vitro. TVF had a M, of ≈ 250 kDa by gel filtration, ≈50 kDa by SDSPAGE, and was heat (56°C, 30 min) and pH (>6 or <8) labile. Co-incubation of TVF with adherent target cells caused a marked rounding and clumping of BHK-21 or CHO-K1 cells, but had no effect on RK-13 or WEHI-3 cells. These morphologic changes were concentration, time, and energy dependent. Reversibility was attained by exogenous serum addition (> 10%) or TVF washout. Target cell perturbations were not accompanied by significant changes in growth (as measured by nuclei counts, DNA content, or 3H-thymidine incorporation), in cell leakage (as assessed by lactate dehydrogenase release), or in cell viability (by trypan blue dye exclusion). TVF-induced effects were independent of cyclic AMP and cyclic GMP levels in BHK cells exposed for 5 min-24 hr.