Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.