As part of a study to evaluate the analgesic efficacy of meperidine and hydroxyzine, alone and in combination, a double-blind complete crossover study of meperidine (50 mg IM), hydroxyzine (100 mg IM), meperidine (50 mg IM) plus hydroxyzine (100 mg IM), and saline placebo was conducted. Thirty patients with chronic moderate to severe pain due to metastatic cancer were evaluated as to pain relief following administration of all four study medications. All of the treatment groups showed statistically significant analgesic activity as compared to placebo. Hydroxyzine provided sustained pain relief to six hours, whereas meperidine produced analgesia up to two hours. The combination produced additive analgesia only during the first 2 hr. The pharmacokinetics of meperidine and hydroxyzine were compared to observed analgesia. Significant correlation between serum drug levels of meperidine and hydroxyzine and pain relief resulted and the serum levels of meperidine and hydroxyzine necessary for analgesia were calculated to be 0.10–0.15 mg/ml and 60–70 ng/ml; respectively. The observed analgesia of the meperidine/hydroxyzine combination was correlated with the analgesia of the individual agents and the limited additive analgesia observed with the addition of meperidine to hydroxyzine does not justify the added toxicity of the narcotic.