A comparison was made of the ability of guinea pig alveolar macrophages, which had been pretreated with hydrocortisone acetate, beclomethasone dipropionate or a corticosteroid substitute pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016, Pivalone), to phagocytose and lyse Staphylococcus aureus or Candida albicans. The three drugs had different patterns of effect on phagocytosis and lysis. Hydrocortisone acetate had little effect on the phagocytosis of Staph. aureus at any dose level tested, but the two higher concentrations slightly inhibited intracellular lysis; phagocytosis of C. albicans was inhibited initially but increased at 5 h. Both beclomethasone dipropionate and tixocortol pivalate caused an initial stimulation of phagocytosis and lysis of Staph. aureus. Ingestion of C. albicans was increased in macrophages pretreated with beclomethasone dipropionate, but their fungicidal activity was unchanged. Pretreatment with tixocortol pivalate stimulated the initial phagocytosis of C. albicans but continued uptake on prolonged incubation was inhibited. Lysis of the ingested organisms was not markedly affected. Since the production of any effect on the phagocytic and lytic activity of alveolar macrophages required much higher levels of tixocortol pivalate than of either of the other two drugs, it is suggested that in clinical use correspondingly higher doses of tixocortol pivalate could be given without danger of affecting either phagocytic activity or the immune response.