Changes in the outflow facility of perfused calf eyes and in the shape of cells in cultured trabecular meshwork (TM) have been studied, following exposure to adrenergic agents and phosphodiesterase inhibitors (PDE). Dobutamine caused confluent TM cells to change their usual polygonal shape to a characteristic stellate shape. Salbutamol had no effect, but PDE inhibitors, isobutylmethylxanthine (IBMX), theophylline, and caffeine were very effective in producing this shape change. Epinephrine, isoproterenol, dobutamine, and salbutamol did not increase the outflow facility, either at 22 degrees C or 36 degrees C, while theophylline, caffeine, and IBMX did increase it in a dose-dependent manner. On the other hand, the high concentrations of beta-adrenergic agents required to produce even a small change in outflow facility and cell shape argue against the involvement of adrenergic-receptor mediation and may suggest another mechanism; on the other, the enhancement of epinephrine effects by PDE inhibitors and the similar effect produced by cyclic adenosine 3',5'-cyclic phosphate (cAMP) and purines suggest that changes in the cell shape are produced by beta-receptor activation. The beta-adrenergic agents were not effective in changing outflow facility, but the PDE inhibitors were remarkably effective both in changing the shape and in increasing facility.