Antral gastrin and somatostatin gene expression during starvation and after refeeding with liquid meals of varying composition were studied. Northern and slot-blot hybridization analyses showed that starvation caused a marked decrease in antral gastrin messenger RNA (mRNA) level by 12 hours associated with an increase in somatostatin mRNA. After 48 hours of fasting, antral gastrin mRNA was 26% and somatostatin mRNA was 136% of their prefasting levels. Refeeding caused increased 2-hour integrated gastrin mRNA levels after liquid peptone (+45%), phenylalanine (+31%), and olive oil (+13%), but no changes were observed with glucose or saline solutions. Integrated 2-hour immunoreactive antral gastrin content was increased after peptone (+106%), phenylalanine (+68%), and olive oil (+32%) meals but was not increased after glucose (-11%) or saline (-10%). In some cases, both gastrin mRNA and peptide responses could be measured as early as 15 minutes. The same nutrients that increased gastrin mRNA levels caused decreased 2-hour integrated somatostatin mRNA levels; peptone (-30%), phenylalanine (-28%), and olive oil (-21%), but neither glucose nor saline, altered somatostatin mRNA levels. These results suggest that antral gastrin and somatostatin genes were regulated in opposite directions, in a coordinate manner, by specific gastric nutrients that stimulate gastrin release. © 1991.