The toxic and irritant principles of the seed oil and of the latex of the caper spurge (Euphorbia lathyris L.) were isolated together with several non irritants of similar chemical structure. From the seed oil two irritant Euphorbia factors L5 and L6 and from the latex a mixture of irritant Euphorbia factors were obtained. Euphorbia factor L5 was identified as 3-hexadecanoate of the new tetracyclic, poly-functional diterpene parent alcohol ingenol. Euphorbia factor L6 most probably is the 3-tetradeca-2,4,6,8,10-penta-enoic acid ester of ingenol. The mixture of Euphorbia factors was shown to contain esters of ingenol and of 16-hydroxy-ingenol, respectively, each containing a long chain unsaturated fatty acid, most probably in 3-position. The non irritants from the seed oil comprise ingenol-20-hexadecanoate (compound L4) and several esters of macrocyclic diterpenes of the new lathyrol type (compounds L1-L3, L8, and possibly L7). Compound L4 is a positional isomer of Euphorbia factor L5 and most probably an artefact formed during the isolation procedure. The macrocyclic diterpenes are of interest as possible intermediates in the biogenesis of tetracyclic diterpene parents of cocarcinogenic esters. The parent alcohols ingenol and 16-hydroxy-ingenol are inactive irritants. As compared to croton oil factor A1 (TPA), Euphorbia factor L5 exhibits about 1/10 of its irritant activity on the ear and about 1/10 of its cocarcinogenic activity on the back skin of mice. As an irritant Euphorbia factor L6 shows about 1/5 of the activity of A1. Structure/activity relationships of ingenol and phorbol esters and the possible role of cocarcinogens of plant origin as second order carcinogenic risk factors are discussed.