Human labial acini were assayed for the presence of ion transport systems associated with salivary fluid secretion using microfluorometric methods. Na(+)-K(+)-Cl- contransport and Na+/H+ exchange activities (determined by their bumetanide and amiloride sensitivities, respectively) were found at levels approximately 50% of those seen in similarly assayed rat parotid acini, but little, if any, C1-/HCO3-exchange activity was observed. Also, when human labial acini were stimulated with the muscarinic agonist carbachol, little evidence of the intracellular acidification associated with HCO3- secretion by other salivary glands was found. Na+/H+ exchange activity in human labial acini was downregulated (approximately 40%) by beta-adrenergic stimulation and upregulated (approximately threefold) by muscarinic stimulation. In contrast, beta-adrenergic stimulation produced only a marginally significant increase in Na(+)-K(+)-Cl- cotransport activity, and muscarinic stimulation was without effect. We include that basolateral Na(+)-K(+)-Cl- cotransport appears to be the dominant mechanism driving Cl- secretion and thereby fluid secretion in this tissue.