We analyzed trends in prescribing and overdose deaths related to propoxyphene (e.g., Darvon) before and after a 1978-80 informational campaign carried out by the US Food and Drug Administration and the drug's manufacturer through mailed warnings, face-to-face education of prescribers, press releases, and labeling changes. The goals included a reduction in propoxyphene use with alcohol or other CNS depressants, reduced prescribing of refills, and cessation of prescribing for patients at risk of abuse and misuse (suicide). We conducted time-series analyses of nationwide propoxyphene use data 1974-83 and analyzed data on drug overdose death rates covering a combined population of about 83 million. Segmented regression methods were used to determine if the informational program was associated with changes in trends of prescribing or overdose deaths. Comparison drug series were analyzed to control for other secular trends in prescribing. Nationwide propoxyphene use during the warnings continued a pre-existing decline of about 8 per cent per year, but this decline halted after the warnings. The no-refill recommendation had no impact on refill rates. The risk of overdose death per propoxyphene prescription filled has remained about constant since 1979. Sharper declines in misuse of such drugs will require stronger, more sustained regulatory or educational measures.