This study examines whether a 10-week period of daily insulin injections following intraportal islet transplantation improves the metabolic state in streptozotocin-diabetic recipients of a suboptimal number of beta cells. In recipients receiving 0.5 million beta cells, insulin treatment increased the number of animals with normal basal glycemia (from 2/6 to 7/8) and normal serum fructosamine (from 1/6 to 6/8). However, during the four weeks following a 10-week insulin regimen, this beneficial effect was lost and no differences were noticed in glucose tolerance curves and hepatic insulin reserves of insulin-treated and untreated recipients. In recipients receiving 1.1 million beta cells, administration of insulin did not influence the number of animals with normal basal glycemia (7/7 in both groups) or with normal serum fructosamine (5/7 versus 4 to 6/7) during the period of treatment or during the subsequent 4 weeks; prior insulin treatment did not improve glucose tolerance curves but reduced the hepatic insulin reserves by one-third. It is concluded that insulin injections can improve the metabolic state in recipients of an insufficient islet mass but do not enhance the metabolic capacity or insulin reserves of a hepatic islet implant. The reduced hepatic insulin content in one group of insulin-treated recipients raises the possibility that supplements of insulin injections reduce the size of grafted insulin reserves.