Multiple signals are involved in the regulation of Ig production by human B lymphocytes. Leukotrienes, especially LTB4, have been shown to inhibit Ig production by increasing the number and function of suppressor lymphocytes. Production of leukotrienes has been demonstrated by mast cells, basophils, eosinophils, polymorphonuclear leukocytes, monocytes, and macrophages. In this paper we demonstrate that a human T-T hybridoma grown at 5 x 10(5) cells/ml constitutively produces 5 ng/ml of LTC4. Furthermore, we demonstrate that either the supernatant from this hybridoma containing 0.5 to 10 ng/ml LTC4 or purified LTC4 in the range of 0.5 to 5 ng/ml can suppress 50 to 70% of Ig production by unfractionated human mononuclear cells, by normal human cells stimulated with Staphylococcus aureus Cowan I and B cell differentiation factors, and by the EBV-transformed B cell line SKW.6 in the presence of B cell differentiation factors. Thus, LTC4 can have direct effects on B cells and may have a role in normal B cell regulation.