We evaluated whether long-term (2 months) administration of interleukin-7 (IL7) hastens immune recovery in baboons rendered severely lymphopenic by total body irradiation and antithymocyte globulin (ATG). Four baboons were treated with recombinant baboon IL7 and three baboons with placebo. Median CD4 T cell count at the end of IL7/placebo treatment was higher in the IL7-treated animals (2262 vs. 618/microl, P = 0.03). This appeared to be a result of peripheral expansion rather than de novo generation. Median cytomegalovirus (CMV)-specific IFNgamma-producing CD4 T cell count at the end of IL7/placebo treatment was higher in the IL7-treated animals (122 vs. 1/microl, P = 0.03). All animals were pretransplant cytomegalovirus-seropositive. One animal died at the end of IL7 treatment; necropsy showed extensive T cell infiltration of kidneys and lungs. In conclusion, IL7 stimulates the expansion of CD4 T cells, including functional antiviral cells. Clinical risk-benefit ratio needs to be evaluated.