During the asymptomatic phase of human immunodeficiency virus 1 (HIV-1) infection the lymphatic tissues seem to function as a major reservoir of HIV. We have examined the viral load in peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) of 12 naturally and 4 experimentally long-term simian immunodeficiency virus (SIV)-infected African green monkeys (AGM) to help explain the apathogenicity of the AGM isolates of SIV (SIV_agm) in their natural host. The mean number of SIV_agmproducing cells determined by limiting dilution assay was found to be 1.7 ± 2.2 and 2.1 ± 3.3 per 10⁵PBMC or LNMC, respectively. Similarly, polymerase chain reaction analysis of serially diluted cells showed the mean provirus carrying cell number to be 2.8 ± 3.7 per 10⁵PBMC and 4.0 ± 5.5 per 10⁵LNMC. When normalized for CD4⁺cells the provirus and infectious virus loads in the LNMC and PBMC were also similar. No trapping of virus particles could be detected byin situhybridization or immunohistochemistry. The data demonstrate that in contrast to HIV-1-infected humans, the viral burden in the lymph nodes of long-term SIV_agm-infected AGMs is comparable to that in the PBMC.