Five lactating mothers were administered the therapeutic dose of zaleplon (10 mg) orally in an open-label, single-dose, pharmacokinetic study. Plasma and breast milk were sampled through 8 hours after dose administration for subsequent determinations of zaleplon and its major, though inactive, plasma metabolite 5-oxo-zaleplon. Zaleplon concentrations peaked in plasma and milk approximately 1 hour after dosing and then disappeared rapidly. The mean terminal half-life was slightly greater than 1 hour. Milk concentrations "mirrored" plasma concentrations closely with no discernible delay between peak times. The average milk-to-plasma (M/P) concentration ratio for zaleplon was approximately 0.50 over the time course. 5-oxo-zaleplon was undetectable in all but one milk sample. The maximum exposure of an infant to zaleplon during a feeding at peak milk concentrations was estimated to range from 1.28 micrograms to 1.66 micrograms, corresponding to 0.013% to 0.017% of the maternal dose or 0.320 microgram/kg to 0.415 microgram/kg for a 4 kg infant. The results indicate that zaleplon taken by a nursing mother is transferred through breast milk to her infant in very small quantities that are unlikely to be clinically important.