It has been suggested that adenylate cyclase activation involves reduction of a disulfide linkage. Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and prostaglandin F2α (PGF2α) were tested for their ability to act as reducing agents with either cytochrome c, or the disulfide 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB), the latter with a catalytic amount of ferric chloride. PGE1, PGE2, and PGI2 significantly reduced cytochrome c while PGF2α did not. PGE1, PGE2 and PGI2 reduced DTNB while PGF2α did not. The results are consistent with the postulate that prostaglandins which are effective in activating adenylate cyclase can act as reducing agents and might be involved in reductive activation of adenylate cyclase.