Simian immunodeficiency virus (SIV) replication is rapidly downregulated in the lymph nodes (LN) of rhesus macaques after the acute stage of primary infection. The aim of this study was to evaluate a possible role of interferon-gamma (IFN-gamma) in the control of SIV replication. IFN-gamma expression was analysed by in situ hybridization in the LN of rhesus macaques that were inoculated either with a high dose or with a low dose of the pathogenic isolate SIVmac 251. The kinetics of IFN-gamma induction in LN was found to follow that of SIV replication. However, the number of IFN-gamma expressing cells was not proportional to the number of infected cells. IFN-gamma expression in LN was further quantified by competitive RT-PCR. The number of IFN-gamma mRNA molecules in LN was high for the animals of the high dose group. In the low dose group, the IFN-gamma copy number varied over 2 log10 units and was particularly low for the animals that had a high and persisting antigenaemia. The analysis of a total of 10 animals inoculated with a low dose of virus showed an inverse correlation between IFN-gamma expression in LN and peak antigenemia (P < 0.01). This study provides evidence for a marked individual variability in the IFN-gamma response to primary SIV infection and supports the notion that IFN-gamma production is inhibited at an early stage in animals that harbour a high viral load.