Guinea-pig assays have been used extensively to detect contact sensitizers. In contrast, almost no reliable assays are available to detect the potential for low-molecular-weight drugs and chemicals to induce systemic allergic reactions in humans. Based on clinical data, and, to some extent, on recent immunological findings, it is proposed that guinea-pig assays can predict the hazard for systemic allergic reactions in man. Seventy drugs and chemicals were compared from published results in guinea-pig assays and in the clinic. A close correlation was found with 43 substances and a relatively good one with 16 substances. Conflicting results were found with 11 substances only. However, substances known to induce systemic allergic reactions in man were all detected as weak sensitizers, at least in guinea-pigs. Guinea-pig contact sensitization assays may therefore prove useful until more suitable and specific assays are available to predict the risk for systemic allergic reactions.