OBJECTIVE: To compare the pain associated with ceftriaxone sodium injections by using two different diluents, ie, lidocaine hydrochloride and sterile water. DESIGN: Prospective study of adolescents who were culture positive for gonorrhea. Random selection of the diluent used for the intramuscular ceftriaxone therapy. SETTING: Urban, hospital-based adolescent medicine service. SUBJECTS: Thirty-nine adolescents and young adults, predominantly of black or Hispanic backgrounds, ranging in age between 14 and 23 years (mean age, 17.6 years; median age, 17 years), of whom 27 were females. METHODS: Pain predictions were elicited from the adolescents before treatment. Pain ratings were obtained at five time intervals after the injections. All ratings were obtained by using a visual analog scale. RESULTS: No pain prediction differences before the injection were noted between the two groups. Individual t tests showed significant pain differences between the two groups at the time after the injection and at 10- and 20-minute and 6-hour intervals. Repeated-measures analysis of variance models showed that the diluent effect on pain was significant. CONCLUSION: Lidocaine can reduce the amount of pain of an intramuscular injection of ceftriaxone when compared with sterile water as a diluent. These findings have implications not only for the treatment of gonorrhea but also for other situations where intramuscular injections utilizing a diluent may be necessary.