In the present study the apoptotic fraction has been investigated in peripheral blood mononuclear cells (PBMCs) and in lymphoid tissue of six clinically asymptomatic serologically positive specific pathogen free (SPF) FIV-infected cats with a decline in peripheral blood CD4+ lymphocytes, compared to five FIV- SPF controls. Apoptosis in PBMCs was scored in relation to cell cycle phases judged by the integrating cytometric measure of DNA content with 3H-thymidine and 3H-leucine incorporation. Apoptosis in lymphoid tissue was revealed with the ApopTag-peroxidase kit, quantified by image analysis and expressed as apoptotic index (number of apoptosis per 100 cells). The high percentage of apoptotic death in lymphocytes from FIV+ cats was chronologically related to the entrance of cells in the S phase of the cell cycle (p < 0.0001). No difference in the apoptotic index was revealed comparing the follicular, cortical + paracortical and medullary compartments in lymph nodes of FIV+ and FIV- cats. In each group of cats a similar pattern of apoptosis expression was revealed in lymph nodes: significantly higher in follicular vs. both cortical + paracortical and medullary compartments (p < 0.001). In the thymus a significant increase in apoptotic index was revealed in the cortical compartment of the FIV+ cats compared to FIV- (p < 0.001), while in the spleen both the red and white pulp expressed a higher value in FIV+ cats compared to FIV-(p < 0.05) and the former showed a pattern of expression as follows: in the red pulp significantly higher than in the white pulp (p < 0.001). This investigation suggests that the priming signals for apoptosis in FIV infection parallels the S phase of the cell cycle and peripheral blood changes could follow both thymic and splenic modifications in apoptotic expression.