Crohn's disease (CD) is characterized by granulomatous inflammation of the intestinal mucosa, but the etiology and pathogenesis of the inflammatory lesions are unknown. The aim of this study was to determine whether T-cell activation and lymphokine production occurs in the mucosal lesions of this disease. Total cellular RNA was isolated from peripheral blood lymphocytes and from colonoscopic mucosal biopsies of normal individuals and patients with CD of the colon or ulcerative colitis (UC). Levels of interleukin-2 (IL-2) messenger RNA (mRNA) transcripts in samples were determined using a quantitative reverse transcriptase polymerase chain reaction method. IL-2 mRNA transcripts were detected in histologically normal intestinal mucosal biopsies obtained from control subjects. In CD, higher levels of IL-2 mRNA transcripts were detected in the mucosa from areas of active inflammation, but in areas that were histologically normal, levels were similar to control subjects. The levels of IL-2 mRNA transcripts in biopsies from active and inactive UC were similar to control subjects. Levels of IL-2 mRNA in peripheral blood lymphocytes were low and not significantly different in all groups of subjects. In conclusion, the normal intestinal mucosa contains IL-2 mRNA transcripts and may be an important source of IL-2. Furthermore, the inflammatory lesions of CD, but not UC, have higher levels of IL-2 mRNA transcripts, suggesting that T-cell activation and lymphokine secretion in the intestine may be important in the pathogenesis of CD. These data provide further evidence that the pathogenesis of CD and UC are different.