The objective of the present study was to evaluate the involvement of apoptosis in the development of post-weaning multisystemic wasting syndrome (PMWS) lymphoid-depletion lesions. Twenty-one pigs that were categorized into three different lesional severity stages (S1, n= 5; S2, n = 7; S3, n = 9) and five healthy control pigs (stage S0) were used. From all pigs, samples of thymus, spleen, tonsil, ileum and superficial inguinal lymph node were processed for histological examination, in situ hybridization for porcine circovirus type 2 (PCV2) detection and cleaved caspase-3 (CCasp3) immunohistochemistry for detection of apoptotic cells. PCV2 was quantified in serum samples by using TaqMan real-time PCR. CCasp3 labelling was measured in the different morphological compartments of all lymphoid tissues, using an automated system for quantification. Differences between each tissue compartment and lesional stage were assessed, as well as the correlation between apoptosis, lesional stage and viral load. Overall, the results indicated that the more intense the lymphoid depletion, the lower the rate of apoptosis. In the thymus, the cortex was the area where differences between PMWS-affected and control animals were more evident; it was found that all PMWS-affected pigs had significantly lower rates of apoptosis than the controls. In the secondary lymphoid organs, B-cell areas presented higher rates of apoptosis; similar apoptotic rates were found in this compartment in control and S1 pigs. In S2 and S3, B-cell areas were lost and the apoptotic pattern observed was a diffusely distributed low rate of positive cells. Significantly lower rates of apoptosis between PMWS-affected pigs and the control group were already evident in S1 for the thymus, spleen, superficial inguinal lymph node and Peyer's patches, but not for the tonsils. Apoptotic rates in lymphoid tissues were correlated inversely with viral load in serum and with severity of lesions. In conclusion, the results indicate that apoptosis is not a remarkable feature in PMWS lymphoid lesion development. © 2004 SGM.