We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB-Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients in the placebo and 2 patients in the thymopentin group had antibody titers greater than 10 U/l. In both groups only patients with normal or slightly impaired monocyte function responded to vaccination. Thus, we were not able to demonstrate a beneficial effect of thymopentin on hepatitis B vaccination in nonresponders on chronic hemodialysis. Furthermore, functional tests were not able to identify a subpopulation of uremic nonresponders who would benefit from thymopentin.