The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng/ml blood), but was not significantly different from the results obtained in identically treated blood samples from 50 adults (median: 23; range: 1-93 ng/ml blood). Both the maximum HR and the sensitivity to anti-IgE were dependent on total plasma IgE content. Blood samples with plasma IgE greater-than-or-equal-to 0.5 IU/ml (n = 15) had significantly higher maximum HR than those with plasma IgE < 0.5 IU/ml (n = 82; median: 32 vs. 18 ng/ml blood; p < 0.01). Passive sensitization with IgE-rich atopic plasma increased the maximum HR with anti-IgE only in samples with a plasma IgE content of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood differed from our observations in adult blood, and may represent a maturational phenomenon. The family history of allergy was obtained by a questionnaire, and clinical observations were gathered from patient records. None of these parameters were found to influence HR with any secretagogue. However, HR stimulated by the calcium ionophore A23187 was found to be highly dependent on the storage time of the EDTA-anticoagulated blood samples, which should be carefully controlled.