Mammalian HDC mRNA encodes a protein with a molecular mass of 74 kDa. The reported molecular mass for the purified HDC subunit is 53-55 kDa. Western blot analysis of extracts of rat gastric mucosa and fetal rat liver has revealed the presence of at least three different forms of HDC immunoreactivity, having molecular masses of about 74, 63 and 53 kDa. There is evidence from previous studies that full length rat HDC is enzymatically inactive and that activation requires C-terminal truncation. In the present study we examined the various immunoreactive HDC forms in rat oxyntic mucosa and their response to treatments known to affect the HDC activity. Freely fed rats and hypergastrinemic rats (treated with gastrin or the proton pump inhibitor omeprazole) had higher oxyntic mucosal HDC activity and HDC mRNA level than fasted or untreated rats. The difference in HDC activity was greater than the difference in HDC mRNA level. Western blot analysis confirmed the existence of the 74, 63 and 53 kDa HDC forms in the oxyntic mucosa. All three forms were more abundant in the oxyntic mucosa of freely fed and hypergastrinemic rats than in the mucosa of fasted or untreated rats. Of the three HDC forms, the 63 kDa form was the predominant one, the 73 kDa form was quantitatively insignificant by comparison and the 53 kDa form was at or below the limit of detection in fasted rats. The activity of HDC was well correlated to the amount of the 63 kDa HDC form. Administration of cycloheximide to hypergastrinemic rats (undergoing omeprazole treatment) resulted in a rapid decline of the HDC activity (estimated half-life 1 h and 50 min). The 63 kDa HDC form disappeared with a rate that corresponded to the decline in HDC activity. The two other HDC forms seemed to have a slower turnover. Our findings suggest that the 63 kDa form is enzymatically active. The results do not allow any conclusion as to the functional activity of the 74 and 53 kDa forms.