A fixed dose combination of ibuprofen (400 mg) and paracetamol (325 mg) is by far the most extensively prescribed medicament for a variety of musculoskeletal disorders in India. Following clinical observations that this drug combination induces significant adverse effects, its gastric toxicity was investigated in rats. Ibuprofen (25 mg kg-1 p.o., twice daily x 5 days), paracetamol (20 mg kg-1 p.o, twice daily x 5 days), and a combination of the two, had no significant effect on free and total gastric acidity in pylorus-ligated rats. Ibuprofen induced visible gastric ulceration whereas paracetamol did not. However, the combination of these two drugs had an additive effect inducing severe gastric erosions, ulcerations and bleeding. The augmented toxicity of this drug combination appeared to be a consequence of attenuated gastric mucin activity and reduction in the gastric muco-protective barrier. This investigation indicates the likely hazard of an irrational fixed dose drug combination.