There is evidence that the growth of malignant B lymphocytes e.g. hairy cells is regulated by cytokines. Several investigators suggested that the stimulating cytokines are produced by the malignant B cells indicating an autocrine growth regulation. Here we demonstrate that T lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth stimulating T cell clones derived from peripheral blood is identical in patients with hairy cell leukemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B-lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alfa but not antibodies against tumor necrosis factor alfa or interleukin-2 inhibit completely the growth stimulating activity. We propose that interferon alpha inhibits the production of soluble mediators produced by normal T-cells. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells.