Abstract Therapeutic concentrations of salicylate enhanced or inhibited human lymphocyte PHA transformation, depending on the conditions of culture. Responses to salicylate were influenced by serum and cell concentration, PHA mitogenic activity and concentration. In particular, pre-incubation of the mononuclear cell population, in salicylate-free medium made lymphocyte transformation more susceptible to inhibition. The results suggest that the inhibitory effect of salicylate on lymphocyte transformation may be mitigated by a factor released from adherent mononuclear cells. The extent to which culture conditions influence the results of this test emphasise its limitations for assessing the effects of drugs on lymphocyte function in vivo.