Primary infections of Heligmosomoides polygyrus were studied in adult male CD1 mice fed on isoenergetic synthetic diets containing either 2% or 20% protein (casein). A slight reduction in food intake was observed during infection, and this was unaffected by diet. Protein deficiency was also found to have no effect upon worm establishment. Evidence was found, though, to suggest that the worms have a more severe effect upon the host in protein-deficient mice. Hypoalbuminaemia was observed due to diet and also infection, and this was synergistic. There was an increase in non-albumin plasma protein during infection which was not effected by diet. The circulating urea concentration was reduced during protein deficiency, as was the level of essential amino acids, but non-essential amino acid levels were raised. An increase in the levels of urea and essential amino acids was observed at day 4 of infection in mice on the 20% diet, but not on the 2% diet. Splenic atrophy occurred during infection, but the splanomegaly that occurred early during infection was proportionally greater in protein-deficient mice. These results are discussed in terms of the pathophysiology of both protein deficiency and infection, and comparisons are made with human malnutrition syndromes.