Monocytes, separated from human peripheral blood, were preincubated with different polycyclic aromatic hydrocarbons (PAHs) for 24 h and the production of superoxide ions (O*2-) was then measured using as a stimulating agent phorbol 12-myristate 13-acetate. A significantly enhanced O*2- production is only observed when the cells are treated with benzo[a]pyrene (B[a]P); benzo[e]pyrene, benzo[a]anthracene and 3-methylcholanthrene induce a small but not significant increase of O*2-. Anthracene has no effect, while phenanthrene slightly inhibits. The priming activity of B[a]P is unrelated to variations in intracellular Ca2+ ([Ca2+]i), as demonstrated by the inability of B[a]P to increase [Ca2+]i concentration in both monocytes and the promonocytic cell line U937. Furthermore, in monocytes the sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase inhibitor, thapsigargin, which can increase [Ca2+]i evokes a differentiation-like event associated with a decrease in the production of superoxide ions. These results further support that the enhancing activity of B[a]P on monocytes superoxide production is not mediated by an increase of [Ca2+]i. In contrast, the role of the aryl hydrocarbon receptor (AhR) in B[a]P-induced superoxide ion enhancement is suggested by the inhibitory effect of the specific antagonist alpha-naphthoflavone (alphaNF), while the tumor necrosis factor (TNF-alpha) is not involved in the phenomenon. Thus, the interaction of B[a]P with its cytosolic receptor and either the metabolism of the compound into reactive intermediates or the over-expression of some unknown genes seem to be involved in an essential step in this process.