AbstractSpleen cells fromNippostrongylus brasiliensis‐infected mice produce large amounts of histamine in response to adult worm antigen. This phenomenon results from the production of HCSF (histamine‐producing cell‐stimulating factor, probably related to IL3) by sensitized lymphocytes. This factor acts on its target cells (presumably mast cell precursors) by inducing a rapid increase in histamine synthesis. Similarly, parasite infection generates enhanced histamine production by spleen cells in response to concanavalin A (Con A). This results from increases in both HCSF production and the HCSF sensitivity of its target cells. In all cases, maximal histamine and HCSF productions are obtained on day 8 after infection and coincide with parasite rejection. Methyl prednisolone suppresses HCSF production by infected mouse spleen cells in response to worm antigen or Con A. HCSF activity is foundin vivoon day 8 in the sera of infected mice, 4 h after they are challenged with an i. v. injection of adult worm antigen. No activity is detected in the sera of normal mice with or without antigen injection. Sera from infected mice that did not receive the antigen exhibit a slight HCSF activity on day 8. Our data bring the first evidence of the existence of anin vivoproduction of