Jet injection has met with great success in the rapid and effective mass administration of several immunizing agents. The recent development of a jet injector nozzle specifically designed for intradermal inoculation suggested the possible extension of jet injector methodology to mass smallpox vaccination. A total of 156 volunteer subjects, 16 unvaccinated and 140 vaccinated more than 5 years previously, received either undiluted smallpox vaccine by the multiple-pressure technique, or 0.1 ml of various dilutions of smallpox vaccine by jet injector using the new nozzle. Cutaneous and serological responses in revaccinees revealed that jet injection of diluted vaccine with a titre of 10(7) TCID(50)/ml was as effective as multiple-pressure inoculation of undiluted vaccine. Among the small number of primary vaccinees, jet injection of diluted vaccine with a titre of 10(6) TCID(50)/ml appeared as effective as multiple-pressure inoculation of undiluted vaccine. No complications of vaccination occurred.The findings confirm the utility of the intradermal nozzle for jet injection of smallpox vaccine. In view of the speed of administration and the economy of vaccine, it is suggested that there is a distinct role for jet injection in global smallpox eradication efforts. Further studies on larger numbers of unvaccinated subjects and on persons with significant residual vaccinial immunity are needed to define the optimal concentration of vaccine for mass vaccination by jet injection.