The peptide substance P has been recognized for years as having dramatic effects on such diverse physiological responses as blood pressure regulation, peristalsis of the gut, and salivation. More recently, demonstration of substance P receptors on leukocytes and modulation of leukocyte functions by this peptide suggested that it might also have a role in immune regulation. This review focuses on the growing body of evidence that demonstrates substance P-induced effects on one population of leukocytes, namely B lymphocytes. Despite the diversity of experimental techniques used, there is surprisingly good agreement as to the role substance P has in modulating B lymphocyte responses. In vivo treatments of rodents, which increase substance P concentrations in the periphery, increase the number of immunoglobulin-secreting cells in these animals. Conversely, infusion of substance P antagonists or depletion of substance P-containing neurons in rodents substantially reduces the animals' ability to synthesize immunoglobulins. With the use of cultures of B lymphocytes it was possible to demonstrate similar results. In the presence of polyclonal B cell activators, substance P augmented immunoglobulin secretion in cultures of purified B lymphocytes or B cell clones. The absence of accessory cells in these cultures suggested that substance P could act directly on activated B lymphocytes, and in fact these B cells were shown to express specific receptors for this peptide. It appears that the substance P receptors expressed by leukocytes are similar or identical to those expressed by neurons as evidenced by radioreceptor binding assays and detection of the gene encoding the substance P receptor.(ABSTRACT TRUNCATED AT 250 WORDS)