Transformation of agricultural crops with novel genes has significantly advanced disease-resistance breeding, including virus resistance through the expression of virus sequences. In this study, the effects of long-term, repeated exposure to transgenic papayas carrying the coat protein gene of Papaya ringspot virus and conventional non-transgenic papaya on the histology and selected biochemical parameters of the intestinal tract were compared. For 3 months, male and female Wistar rats received diets containing transgenic or non-transgenic papaya at twice the equivalent of the average daily consumption of fresh papayas. Gross and macroscopic appearance of intestinal tissues, as well as stomach tissues, was comparable (P &lt; 0.05) as were total intestinal bacterial counts and activities of beta-glucuronidase. Activities of disaccharidases were not affected, neither were those of amylase (P &lt; 0.05). Although significant differences were noted in the activity of Ca2+ and Na+/K+ ATPase brush border enzymes, no morphological alteration in the integrity of the intestinal mucosa was found. Overall, negligible effects on feed intake, body weight, and fecal output were observed (P &lt; 0.05). Taken together, long-term exposure to diets formulated with transgenic papaya did not result in biologically important unintended effects.