Forskolin and 18 chemical analogs of forskolin were assayed for stimulation of adenylate cyclase activity in vitro and for their effects on intraocular pressure (IOP) in vivo. Adenylate cyclase activity was determined with a preparation of corpora striata from male Wistar rats and test drug concentrations of 0.3 to 300 microM. IOP effect was monitored after a single topical ocular application of a 1% suspension of the test drug to male New Zealand albino rabbits. Significant reductions in IOP occurred with compounds which had potent cyclase stimulatory properties. Most compounds with little cyclase stimulatory effect produced little or no decrease in IOP. A 1-substituted morpholino-acetoxy derivative, which may be a prodrug metabolized to active form by corneal esterases, showed little cyclase stimulation in vitro but produced significant reductions in IOP.