As normal mice do not respond to interleukin-13 (IL-13), we have used mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice) as an in vivo model for studying human IL-13. PBL from three donors (two allergic and one non-allergic) were prestimulated with IL-13 in vitro and thereafter transplanted into SCID mice. As evidenced by flow cytometry, IL-13 in the in vitro cell cultures was physiologically active and suppressed CD14 expression, while it enhanced the expression of CD23 on human monocytes. In the in vivo experiments, SCID mice transplanted with cells from both allergic donors produced twice as high maximum levels of IgE when the cells were preincubated with IL-13 in vitro before transplantation, as compared with mice receiving cells that had not been preincubated with IL-13. Two succeeding intraperitoneal (i.p.) injections of IL-13 resulted in a further increase of maximum IgE levels. Using cells from the non-allergic donor, no enhancing effect of IL-13 was observed. Transplanted human cells from one allergic donor examined were shown to migrate to the spleen and lungs of the recipient mice, while cells from the non-allergic donor were found only in the peritoneal cavity. Altogether, our results indicate that IL-13 enhances human IgE production in vivo and suggest that lymphocytes in allergic individuals are hyper-reactive to this cytokine. Furthermore, the allergic status of the cell donor may affect migration and engraftment of cells transplanted into SCID mice.