Serum and urine specimens of 31 patients with suspected lysergic acid diethylamide (LSD) intoxication were analyzed for LSD by both radioimmunoassay (RIA) and high-pressure liquid chromatography (HPLC). The RIA assay, using 0.1 ng/mL as the limit of detection instead of the manufacturer's recommendation of 0.5 ng/mL, was positive for LSD in 13 blood and urine specimens from 14 patients. Results were compared to HPLC analysis using methysergide instead of lysergol as the internal standard and a limit of detection of 0.5 ng/mL. HPLC detected LSD in 9 of 13 serum specimens and 11 of 13 urine specimens that had tested positive by RIA. Of 18 patients with a final clinical diagnosis of LSD intoxication, LSD was detected by RIA in 14 patients and by HPLC in 11 patients. For 13 other cases in which the final diagnosis was a condition other than LSD intoxication, serum and urine assays for LSD were negative in all cases by both techniques. LSD assays have not been generally available in clinical laboratories. We conclude that the qualitative determination of LSD in either serum or urine by a commercially available radioimmunoassay has made it possible to provide reliable laboratory confirmation of LSD intoxication.