Although there is compelling evidence that amiloride reduces the intensity of Na+ and Li+ salts in humans, its effects on saltiness are conflicting. Many salts elicit not only a salty taste but also one or more side tastes (sweetness, sourness or bitterness). Some studies have shown a suppression of saltiness by amiloride; others show no effect on saltiness but a significant reduction in sourness. In the experiments demonstrating a reduction of saltiness, subjects estimated only saltiness; in those showing an amiloride effect on sourness and not saltiness, subjects estimated all qualities on each trial. The present study examines the role of the psychophysical method in these conflicting results. We have investigated the effects of amiloride on taste quality by modifying only the instructions to the subjects, keeping all other variables constant. One group of subjects (intensity-only) gave magnitude estimates of the overall intensity of a LiCl concentration series. A second group (salty-only) was instructed to estimate the saltiness of the stimuli, and a third group (sour-only) estimated their sourness. Finally, a fourth group (profile) rated all of the taste qualities on each stimulus presentation, using a modified taste profile method. The ratings of all groups were made comparable by the use of 0.1 mM quinine-HCl as a modulus. When subjects used only one response category, amiloride reduced their estimates (of intensity, saltiness or sourness), but if subjects attended to all four qualities, amiloride specifically reduced the sourness of LiCl and had no significant effect on its saltiness. Comparison of the saltiness estimates of the salty-only group to the sum of the salty and sour estimates of the profile group demonstrated that subjects combined these sensations when presented with only one response alternative. To reveal the effect of amiloride on a specific quality of a salt, the psychophysical method must allow subjects to attend to all qualities on each trial. These data and previous results suggest that apical Na+ channels on the taste receptor cell membrane mediate the sourness but not the saltiness of Na+ and Li+ salts.