Performance decrements associated with therapeutic drugs may increase the risk of many common activities that require intact skills. However, accident data that define such risks are difficult to obtain, and the assessment of skill decrements often must be based on data obtained from the laboratory study of drug- effects. The validity and reliability of conclusions drawn from laboratory data are a function of experiment design and measurement methods. Critical issues include the assumptions, rationale, and hypotheses underlying laboratory measurement of skills performance. Drug doses and dosing regimens, subject characteristics, and response measures are key variables that limit data interpretation. The design of reported experiments, including the selection of a battery of laboratory tests, reveals the underlying issues, and data from the experiments demonstrate both valid conclusions and constraints on intepretation. © by American College of Occupational Medicine.