Experiments with pigs have been performed to establish bone marrow chimerism and skin graft tolerance between SLA genotyped animals. Recipients were conditioned by means of fractionated partial irradiation from lateral cobalt sources (partial lateral irradiation (PLI)). The head, neck, and lungs were protected with lead, the rest of the body being irradiated including the thymus, the majority of lymphoid organs with spleen, and most of the bone marrow sites. Four irradiation protocols were tested: A = 100 cGy χ 17 times PLI over 25 days completed by one final 100 cGy of total body irradiation; B = 300 cGy χ 6 times PLI over 12 days; C = 435 cGy χ 6 times PLI over 12 days; C = 435 cGy χ 6 times PLI over 18 days; and D = 650 cGy χ 4 times PLI over 12 days. Bone marrow cells were injected 24 hr after the last irradiation, followed 1 day later by skin grafts; either autologous, or from the bone marrow donor (specific graft), or from SLA-compatible (compatible control) or incompatible donors (incompatible third-party graft). Experiments were performed with SLA-semi-incompatible donor-recipient pairs. No detectable bone marrow chimerism was ever obtained in this situation whatever the protocol used. However, significant prolongation of the specific skin graft (21.4 days) was obtained with protocol B (incompatible third-party graft, 10 days). On the other hand, SLA-compatible donor-recipient pairs were studied using protocol B. Successful establishment of a permanent bone marrow chimerism and perfect tolerance of the specific skin graft after 5 months was obtained. Fifty per cent of the ctlls in the bone marrow and peripheral blood were of donor origin. No sign of graft-versus-host reaction was observed in this SLA-compatible situation. Our results with incompatible pigs do not agree with earlier work in rodents and dogs. Possible reasons for these discrepancies are discussed.