Morphine and meperidine distribution in the neuroaxis were studied in rats after intrathecal injection through catheters ending at the lumbar level.14C-Morphine and3H-meperidine were injected with pharmacologic doses of each drug. Radioactivity was measured in spinal cord segments at different times. At 14 min the segment with maximum morphine concentration (T11–12) contained 8.6 ± 2.4 (mean ± SD) pmol/mg, a value 215 times higher than would be observed if distribution in the body were homogeneous. The ratio between concentration in the most rostral segment (C3–4) and in the segment with maximal concentration was 0.21 ± 0.10. At 14 min the segment with maximum meperidine concentration (T9–10) contained 161.4 ± 33.9 pmol/mg wet tissue, a value 75 times higher than would be seen with even distribution in the body. The ratio (C3–4vs.T9–10) was 0.10 ± 0.04 at this time.The distribution of14C-morphine in the whole central nervous system (CNS) was studied in mice by whole body autoradiography after intrathecal injections of 5 μl at the L5–6 level. High levels of radioactivity were detected in the whole spinal cord and in brain regions close to the basal cisterns until 2 h after injection. At 4 h only the caudal part of the spinal cord had detectable levels of radioactivity.The per cent of the injected dose of morphine that was recovered from the spinal cord was 26.5 ± 4.5 at 14 min, 19.9 ± 8.8 at 44 min, and 4.5 ± 1.7 at 179 min after injection. The figure was 6.9 ± 1.8 at 14 min and 2.2 ± 0.7 at 44 min for meperidine. It could be postulated that the hydrophilic drug morphine persists for longer in the spinal cord, whereas the lipophilic meperidine is rapidly taken up and eliminated, resulting in lower recovery. The spread of morphine into the basal cisterns is consistent with the clinical risk of ventilatory depression.