The irritant and tumor-promoting principles were isolated from the latex of Euphorbia resinifera Berg. and from the resin derived from latex (euphorbium), which is commercially available as a drug. The irritant Euphorbia factors RL 5 (mixture), RL 6, RL 7, RL 8, and RL 10 were identified as tigliane-type 12-deoxyphorbol esters each bearing, in the 13 position, either long-chain, partially methyl-substituted acyl residues (10-16 carbon atoms) or short-chain acyl residues (4 or 5 carbon atoms) or a (substituted) phenylacetyl group with a 20-acetoxy group. Euphorbia factors RL 15 (mixture), RL 16, RL 17, RL 18, and RL 21 are the corresponding 20-deacetylated derivatives thereof. The irritant Euphorbia factors RL 11, RL 12, RL 22, RL 23 were characterized as esters of the tigliane type 12-deoxy-16-hydroxyphorbol, i.e., 13-0-phenylacetyl-16-0-benzoyl-12-deoxy16-hydroxyphorbol-20- acetate (RL 11) and 13, 16-0-phenylacetyl, tigloyl-12-deoxy-16-hydroxy-phorbol-20-acetate (RL 12), RL 22 and RL 23 representing the respective 20-deacetylated derivatives. A mixture of irritant factors, RL 13, was shown to represent long-chain 3-esters of ingenane-type ingenol with similar acyl residues (10-16 carbon atoms, partially methyl-substituted) to RL 5 (RL 15) above. A further group of E. resinifera factors was of the daphnane type: RL 9 was identified as the extremely irritant 9,13,14-orthophenylacetate of resiniferonol-20-(4-hydroxy-3-methoxy)phenylacetate (Resiniferatoxin), RL 14 as the corresponding 9,13,14-orthophenylacetate of resiniferonol, and RL 20 as 14-0-phenylacetylresiniferonol-20-(4-hydroxy-3-methoxy)-phenylacet ate (Proresiniferatoxin). The irritant factors specified below were accompanied by nonirritant esters of the tigliane type 12,20-dideoxyphorbol, i.e., RL 1 and RL 2, and of the lathyrane type ingol, i.e., RL 3 and RL 4. In tumor promotion experiments the mixture of homologous irritant factors RL 13 was equipotent with the standard tumor promoter TPA, but at 10 times the dose of TPA. Several others of the irritant factors had low activity as tumor promotors, but of the few tumors obtained in these experiments a high percentage was malignant. The very high irritant activity of the latex may be ascribed to resiniferatoxin (RL 9), representing a new class of rapidly acting skin irritants. No promoting activity was detected on administration of the highly irritant resiniferatoxin.