Factors influencing the release of histamine by basophils exposed to the radiocontrast agent diatrizoate were investigated in vitro by use of cells from healthy adult subjects with no history of radiocontrast reactions. Diatrizoate-induced release shared similarities with calcium ionophore-induced release. The response to both agents is dose dependent, enhanced by deuterium oxide, optimal at 37 degrees C, calcium dependent, and enhanced with longer reaction times. Unlike calcium ionophore, however, pretreatment of basophils with diatrizoate may also induce dose-dependent inhibition of reactivity during subsequent challenges with anti-IgE, N-formyl methionine peptide, and calcium ionophore. These findings suggest that diatrizoate may induce histamine release via a calcium ionophore-like mechanism, but other effects on cellular function probably account for its ability to inhibit basophil responsiveness.