Identifying diet-disease relationships in nutritional cohort studies is plagued by the measurement error in self-reported intakes. The authors propose using biomarkers known to be correlated with dietary intake, so as to strengthen analyses of diet-disease hypotheses. The authors consider combining self-reported intakes and biomarker levels using principal components, Howe's method, or a joint statistical test of effects in a bivariate model. They compared the statistical power of these methods with that of conventional univariate analyses of self-reported intake or of biomarker level. They used computer simulation of different disease risk models, with input parameters based on data from the literature on the relationship between lutein intake and age-related macular degeneration. The results showed that if the dietary effect on disease was fully mediated through the biomarker level, then the univariate analysis of the biomarker was the most powerful approach. However, combination methods, particularly principal components and Howe's method, were not greatly inferior in this situation, and were as good as, or better than, univariate biomarker analysis if mediation was only partial or non-existent. In some circumstances sample size requirements were reduced to 20-50% of those required for conventional analyses of self-reported intake. The authors conclude that (i) including biomarker data in addition to the usual dietary data in a cohort could greatly strengthen the investigation of diet-disease relationships, and (ii) when the extent of mediation through the biomarker is unknown, use of principal components or Howe's method appears a good strategy.