The in vitro production of prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) in response to viable Candida albicans, histamine, and C. albicans plus histamine was examined. With PBMC from 10 healthy women, C. albicans but not histamine induced PGE2 at a low level (100 pg/ml). However, C. albicans plus histamine acted synergistically to stimulate PGE2 production (448 pg/ml). PBMC from 8 of 10 women with recurrent candidal vaginitis also produced maximal levels of PGE2 in the presence of C. albicans plus histamine. Production of tumor necrosis factor by PBMC from patients and controls was unaffected by histamine in both the presence and absence of C. albicans. However, unlike the controls, PBMC from six of the patients who were atopic and from two nonatopic patients spontaneously released PGE2 in vitro. Addition of 4 or 10 units/ml interferon-γ inhibited spontaneous and C. albicans-induced PGE2 production by PBMC. These data reinforce the evidence that immediate hypersensitivity responses may be involved in the etiology of recurrent candidal vaginitis.