Diurnal variation in the intestinal toxicity of 5-fluorouracil in the rat.

1. Water absorption rates by small intestine in vitro and the incidence of diarrhoea in vivo were estimated after 5-fluorouracil was injected into rats at various times of day and night. 2. Impairment of water absorption and the incidence of diarrhoea were minimal in rats on a normal dietary regimen when the 5-fluorouracil was injected at around 02.00 hours. 3. The DNA content of the mucosa of the small intestine from uninjected animals also showed a diurnal variation, with a maximum at around 03.00 hours. 4. Manipulation of the time of injections (possibly in relation to feeding time) provides a potential means for increasing the therapeutic value of 5-fluorouracil.