The uptake and transport kinetics of manganese (Mn) were investigated in the human intestinal Caco-2 cell line both from the absorption side (apical to basolateral) and from the exsorption side (basolateral to apical). With regard to the former, transport versus time revealed (as uptake) a biphasic pattern with an initial transient phase followed by steady-state conditions. Uptake versus Mn concentrations showed saturation-type kinetics with a 100% increase of Mn binding capacity when measurements were made from 0.5 to 2 h of incubation. The transport characteristics in steady-state conditions exhibited two components, saturable (Vmax = 3.70+/-0.07 nmol/cm2/h, K(m) = 32.2+/-3.4 microM) and nonsaturable (slope = [1.4+/-0.2] x 10(-6)cm(-2)/h) usually presumed to reflect transcellular (carrier mediated) and paracellular (diffusional) pathways, respectively. Mn fluxes were decreased by calcium and calcium antagonists, almost 100% inhibited at 4 degrees C, and affected by quinacrine and ouabain. The inhibition of ATP synthesis was apparently ineffective. From the exsorption side, the Mn fluxes, without a transient period, had an approx 20-fold smaller rate than in the absorptive direction and showed mainly a nonsaturable route (slope = [0.6+/-0.1] x 10(-6) cm(-2)/h). The mechanisms participating in the Mn movements through the monolayer are discussed and proposed to be in common, at least partly, with other divalent cations such as calcium, zinc, or iron.