The construct validity of a quantitative work productivity and activity impairment (WPAI) measure of health outcomes was tested for use in clinical trials, along with its reproducibility when administered by 2 different methods. 106 employed individuals affected by a health problem were randomised to receive either 2 self-administered questionnaires (self administration) or one self-administered questionnaire followed by a telephone interview (interviewer administration). Construct validity of the WPAI measures of time missed from work, impairment of work and regular activities due to overall health and symptoms, were assessed relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity and global measures of work and interference with regular activity. Multivariate linear regression models were used to explain the variance in work productivity and regular activity by validation measures. Data generated by interviewer-administration of the WPAI had higher construct validity and fewer omissions than that obtained by self-administration of the instrument. All measures of work productivity and activity impairment were positively correlated with measures which had proven construct validity. These validation measures explained 54 to 64% of variance (p < 0.0001) in productivity and activity impairment variables of the WPAI. Overall work productivity (health and symptom) was significantly related to general health perceptions and the global measures of interference with regular activity. The self-administered questionnaire had adequate reproducibility but less construct validity than interviewer administration. Both administration methods of the WPAI warrant further evaluation as a measure of morbidity.