Changes in L-alanine transport in plasma membrane vesicles from livers of control and 24- and 48-h starved adult rats and the sensitivity of alanine uptake to sulfhydryl group reagents [N-ethylmaleimide (NEM) and p-chloromercuribenzenesulfonate (p-CMBS)] were studied. The portal concentration of certain amino acids was measured, and the relationship between L-alanine transport kinetic parameters and amino acid levels was analyzed. Starvation only induced a decrease in portal concentration of those amino acids that are mainly carried by Na+-dependent systems (85 and 61% for 24- and 48-h starved rats, respectively). Portal alanine concentration was lower in 24-h starved animals than in control rats (370 vs. 587 mu M) and further decreased after 48 h of fasting (228 mu M) Starvation induced an increase in maximum velocity (V-max) values of Na+-dependent L-alanine transport (7.19, 8.97, and 12.38 pmol . U 5'-nucleotidase(-1). 10 s(-1) for control and 24- and 48-h starved rats, respectively) with slight, but not significant, changes in the apparent Michaelis constant (K-m) values (3.35, 2.63, and 2.20 mM for control and 24- and 48-h starved rats, respectively). Portal alanine showed a directly close correlation with K-m values and inverse with V,, values. The mean affinity constant values for the effects of NEM and p-CMBS on Na+-dependent L-alanine transport were lower in 48- (2.57 and 0.13 mM, respectively) and 24-h starved rats (3.59 and 0.32 mM, respectively) than in control rats (8.56 and 0.59 mM, respectively) and showed a directly strong correlation with kinetic characteristics of L-alanine transport and portal alanine concentration. The results of this study suggest that starvation-induced increase in L-alanine transport in liver plasma membrane vesicles is related to changes in the sensitivity of Na+-dependent L-alanine transport to sulfhydryl group reagents.