A study was performed to investigate the local penetration into the nail, the systemic absorption into the rest of the body, and the routes of excretion of sodium pyrithione following topical application to the nail. Approximately 20 μ1 of a film-forming 3% sodium 14C-pyrithione solution was applied once daily to 5 fingernails and 5 toenails of 4 rhesus monkeys for 6 or 7 days. Following dose removal on study day 7, 2 animals were sacrificed, and the treated nails were analyzed for radioactivity. The other 2 monkeys received the topical dose for 1 more day and were monitored during the postdosing period. Sodium 14C-pyrithione was absorbed slowly into and across the nail following topical application, with the nails serving as reservoirs for the drug. Further evidence of the slow movement of sodium pyrithione across the nail was provided by peak plasma 14C equivalents obtained on day 9, 1 day after the last dose had been removed from the nails. Only slight drug concentrations were measurable in plasma, with no radioactivity observed beyond day 12. The urinary excretion data exhibited a delay in peak urinary excretion (days 8 and 9), and an elimination half-life of 2 days, so that approximately 90% of the absorbed drug was eliminated within 1 week following treatment. Including a minor excretion pathway through the feces, total excretion as a percent of dosage was 8.5 %, indicating that less than 10% of the applied topical dose of sodium pyrithione was absorbed systemically. Because monkey and human nails have similar absorptive characteristics, it is likely that corresponding levels of sodium pyrithione equivalents would be absorbed across human nails treated with sodium pyrithione.