To date, encapsulated grafts have usually been implanted in the peritoneal cavity. This site is, however, not ideal, mainly because of its low blood supply. We have investigated the feasibility of intra-portal injection of (400 microm) microcapsules in the pig. Ten-thousand microcapsules per kilogram body weight were injected into six Large White pigs. Portal pressure, various biological tests, portographies and liver histology were recorded before and at various time points after injection. As a result, portal pressure increased after injection (15+/-2.3 vs 8.7+/-1.7 mmHg) but remained within an acceptable range (<20 mmHg) and returned to normal values at 3 months (8.5+/-3.7 mmHg). During the 3-month follow up, liver function and liver tests remained stable. Portographies showed a homogenous implantation of the capsule, with the portal flow always directed to the liver. At histological examination after 3 months the capsules demonstrated various degrees of fibrosis. We can thus conclude that these results demonstrate that intra-portal injection of microcapsules is feasible in a large-animal model. Hemodynamic, biological and radiological results are similar to those observed in clinical free-islet transplantation.