Malnutrition and dehydration are the immediate consequences of diarrheal diseases. To investigate the biological significance of glutamine, alanine and glucose in the intestinal mucosa, we have used Ussing chambers to determine electrolyte transport by measuring short-circuit current (Isc), potential difference (PD) and tissue resistance (TR) in rabbit intestinal mucosa. Increasing doses (10(-5) M to 10(-1) M) of glutamine, alanine and glucose cause a significant increase in intestinal cation cotransport. Although glucose had a slightly earlier effect, 30 mM glutamine and 0.1 M alanine had a maximal effect which was more than two times that caused by 30 mM glucose. The pD2 values for glucose, glutamine and alanine were 3.0, 2.5, and 2.0, respectively. The dose-response curves of these substrates suggest that the intestinal cotransport kinetics for glutamine is different from that of glucose and alanine. Our results demonstrate that all three substrates cause a significant increase in Isc or PD, suggesting an increase in the intestinal mucosa cation cotransport. Glutamine has a larger effect on cation cotransport than alanine and glucose. These combinations should be studied further for the development of an oral rehydrating solution for diarrhea treatment which could prevent the resulting malnutrition, especially in those cases of prolonged diarrheal diseases.