Abstract Nine compounds, based on four biogenetically-related polycyclic diterpene skeletons, were subjected to open and closed patch testing on human volunteer subjects. The tigliane esters phorbol-12, 13, 20-triacetate, 12- O-2 Z-4 E-octadienoyl-4-deoxyphorbol-13-acetate and 12- O-tigloyl-4-deoxyphorbol-13-isobutyrate, in increasing order of potency, produced symptoms of toxicity in closed patch tests, with the dose of the most potent compound in this series being 0.5 μg in 5 μl acetone. Phorbol, a tigliane alcohol, was inactive in closed tests at a dose level of 50 μg/5 μl. The daphnane derivative, daphnetoxin, produced bullae and vesiculation in closed patch tests, but daphnetoxin-5,20-diacetate was devoid of these effects when applied at 10 times the dose of daphnetoxin. The ingenane compounds, ingenol-3,5,20-triacetate and 20-deoxy-16-hydroxyingenol-3,5,16-triacetate, and the lathyrane compound, ingol-3,7,8,12-tetraacetate, were obtained from the hydrolyzed, acetylated irritant latex of Euphorbia hermentiana. At the doses tested, ingenol-3,5,20-triacetate was the only compound derived from this plant to exhibit irritant activity in closed patch tests. In contrast, this compound is inactive as an irritant to the mouse ear at doses up to 250 μg/ear. Only three compounds, 12- O-2 Z-4 E-octadienoyl-4-deoxyphorbol-13-acetate, 12-O-tigloyl-4-deoxyphorbol-13-isobutyrate and daphnetoxin, produced dermatological toxicity in open patch tests at the doses used. Inflammatory signs and symptoms for several of the compounds under test persisted for over four days in open patch tests and for a week or more after application in closed patch testing.