The latex of Euphorbia tirucalli originating from Madagascar contains as irritant constituents ingenane- and tigliane-type diterpene esters derived from the parent alcohols ingenol and phorbol. The main irritant constituents are isomeric 12,13-acetates, acylates of phorbol as well as 3-acylates of ingenol. As acyl groups, they carry homologous, highly unsaturated aliphatic acids of the general structure CH3-(CH2)m-(CH = CH)n-COOH (m = 2,4; n = 2,3,4,5; total number N of C-atoms = 2n + m + 2). The lack of 4-deoxyphorbol esters in this latex as compared to latex of South African origin is probably indicative of the existence of chemical races of E. tirucalli. In the acyl moiety of phorbol esters investigated in detail, an increasing number of C-atoms or an increasing number of double bonds at a fixed number of C-atoms leads to an increase of irritant activity. As compared to their saturated analogs, corresponding unsaturated phorbol esters exhibit similar irritant activities. On the other hand, by an increasing number of conjugated double bonds in the acyl moieties of phorbol esters, the promoting activity is decreased, thus indicating that irritant activity is a necessary, but insufficient, requirement for promoting activity of phorbol esters. An assessment of a potential carcinogenic risk involved in mass production and handling of the plant should point to the very weak tumor-promoting activity and the chemical instability demonstrated for the diterpene constituents in the latex and hence in all plant parts.