The positive effect of the co-expression of T helper (Th) cell type 2 cytokine interleukin-5 (IL-5) on nef-deleted simian/human immunodeficiency virus (SHIV) replication in vitro has been observed previously. To analyse whether the growth advantage of IL-5-containing SHIV (NI-IL5) in vitro would be relevant in vivo, the virus was inoculated into monkeys. Three rhesus macaques were inoculated intravenously with 10(4) TCID(50) of NI-IL5. Results were compared with those obtained previously from SHIV NM-3rN (intact) and SHIV-dn (nef-deleted)-infected monkeys. Cytokine production, analysed by IL-5 ELISA, showed a twofold increase in IL-5 concentration in the plasma soon after the peak of virus replication. Virus replication and antibody production were greater in monkeys inoculated with IL-5-expressing SHIV than in monkeys inoculated with nef-deleted SHIV without IL-5. These findings show a stimulation of SHIV replication by co-expression of IL-5 and suggest the important role of Th2-type cytokines in human immunodeficiency virus type 1 infection.