Morphine has been determined in serum, cerebrospinal fluid (c.s.f.) and in five brain regions in the rat after a single intravenous dose, using high performance liquid chromatography with an electrochemical detector. In pure solution 50 pg morphine and 200 pg naloxone could be detected. Maximal concentrations of morphine were observed in serum and in most brain regions 5 min after administration of morphine. There was a rapid decline in morphine concentrations during the first 30 min, in serum and in all brian regions studied. The morphine concentration in the c.s.f. was constant for the first 30 min, but 30 min later there was a dramatic increase, suggesting that elimination through the c.s.f. could be an important way of eliminating morphine in the central nervous system.