Concentrations of meperidine and its active metabolite, normeperidine, were measured in plasma of patients receiving the drug for analgesia. Meperidine levels in cancer patients were 0.10 to 0.55 microng/ml 1 h after a dose and were 0.05 to 0.14 in patients in the oliguric period after renal transplantation. Normeperidine levels were 0.05 to 0.28 microng/ml in the cancer patients and 0.13 to 0.36 in the renal failure patients. The ratio of normeperidine to meperidine levels was always higher in the renal failure patients than in the cancer patients. Additionally, two patients receiving multiple doses of meperidine had high normeperidine levels and very high normeperidine/meperidine ratios when they showed signs of central nervous system excitation. These data indicate that normeperidine can contribute to the excitatory effects seen after multiple doses of meperidine and suggest that patients with renal failure are particularly susceptible to this problem.