The effect of alterations in extracellular pH on cellular and humoral immune function is reviewed. Because acidic pH predominates at inflammatory loci and other sites of immune activity, most studies to date focus on the effect of acidic rather than alkaline pH. Investigations on polymorphonuclear leukocytes demonstrate mainly inhibition of chemotaxis, respiratory activity, and bactericidal capacity at reduced pH. Evidence of impaired lymphocyte cytotoxicity and proliferation at acidic pH is also beginning to emerge. Many of the clinical acidoses are accompanied similarly by immunodeficiency. Studies on macrophages and eosinophils are few and inconclusive. A small number of studies demonstrate acid-induced activation of complement proteins and the alternative complement pathway, plus increased antibody-binding to leukocytes at lowered pH. A differential effect of acidic pH on humoral and cellular immunity may, therefore, exist. Increasing recognition of the significance of extracellular pH in relation to immune function warrants further studies in this presently incomplete but rewarding field.