The cardiovascular teratogenicity and embryotoxicity of forskolin, a potent activator of adenylate cyclase, was studied in the chick embryo. The drug was topically applied to the surface of the chorioallantoic membrane in the vicinity of the embryonic heart on the 4th day of incubation (Hamburger-Hamilton developmental stage 24). Cardiovascular malformations were induced in 51% of embryos treated with forskolin doses larger than 1 x 10(-8) mol/egg. Major malformations included remnant of the left 4th aortic arch and ventricular septal defect. These results indicate that forskolin induces cardiovascular malformations in the chick embryo and suggest that increased levels of cyclic 3',5'-adenosine monophosphate produced by forskolin may be related to the malformations observed.