Previous studies have shown that the glyceride derivative, sn‐1,2 ‐isopropylidene‐3‐decanoyl‐glycerol (IpOCOC9), can trigger human leukocyte histamine release. Approximately 25 % of the total cellular histamine content is extruded in the presence of 206 # of IpOCOC9; at 69 μM, however, the secretagogue action of the compound is marginal. The characteristics of the release induced by IpOCOC9are closely similar to those reportedly recorded at hyperosmolar triggering of basophils with mannitol, and in many respects they also mimic those observed at phorbol ester‐induced histamine release. The compound decanoic acid cyclopentyl methylester (DACPME), a structural analogue of IpOCOC9, fails to induce histamine release. IpOCOC9, but not DACPME, stimulates human polymorphonuclear leukocyte cytosolic Ca2+−and phospholipid‐dependent his‐tone III‐S kinase activity (unpublished observations). The secretagogue action of IpOCOC9, has therefore tentatively, at least partly, been attributed to a direct protein kinase C activation. In the present studies, we examined the influence of IpOCOC9and DACPME on histamine release triggered by an ensuing exposure to anti‐IgE, the calcium ionophore A23187, formyl‐methionyl‐leucyl‐phenylalanine (EMLP), or 4β‐phor‐bol 12‐myristate 13‐acetate (PMA). It is shown that IpOCOC9‐treatment of cells results in either enhancement or reduction of the release induced by anti‐IgE or by A23187, whereas FMLP‐induced release is consistently reduced and PMA‐induced release consistently enhanced by such a treatment. Treatment of cells with DACPME enhances but does not reduce anti‐IgE‐triggered release, whereas EMLP‐induced release is not affected. Pretreatment of the cells with other putative protein kinase C activators like PMA, sn‐1‐oleoyl‐2‐acetyl‐glycerol (OAC), 1,2‐dioctanoyl‐glycerol (DiCg) or the glycerol derivative sn‐1,2‐diacetyl‐3‐decanoyl‐glycerol (DiC2OCOC9) affects secretagogue‐induced basophil histamine release according to specific patterns similar to but not identical with those recorded for IpOCOC9and DACPME. Thus, e.g., DiC2OCOC9consistently reduces but does not enhance anti‐IgE‐triggered release. These data show that limited structural changes of IpOCOC9may qualitativel