In a recent study reported in this journal Reiss, Davis, Sideman & Plichta (1963) had shown that the s.c. injection of protein-free pineal extract inhibits the wheelrunning activity of female rats. The present study was designed to examine the effect of injections of melatonin (N-acetyl-5-methoxytryptamine) on the wheelrunning activity of male rats. Male rats were used because the possibility of an interaction of the oestrous cycle with melatonin could thus be avoided. After 3 days in which the rats received daily i.p. injections of 0·9% NaCl solution and were then placed in the wheel in order to adapt to the apparatus, they were injected with either melatonin or saline and tested for 13 days. This procedure was adopted in order to assess the reliability of the inhibitory effect reported by Reiss et al. and also to satisfy the criticism of Eayrs (1954) that measurements of activity before an animal