Metabolic pathways have been elucidated for various chemical and solvent exposures in humans. Clinical laboratory analyses in most chemical and solvent exposures are directed toward identification and quantitation of unchanged substance in serum or whole blood. For example, most laboratories routinely screen for unchanged ethylene glycol in suspected poisonings and quantitate ethylene glycol in positive cases even though toxicity from ethylene glycol exposure (including central nervous system depression, acute renal failure, and elevated anion gap metabolic acidosis) is primarily caused by one metabolite-glycolic acid. One objective of this manuscript is to describe the authors' clinical experience with glycolic acid analysis in ethylene glycol human poisonings. Recommended clinical laboratory tests for small hospitals and toxicology reference laboratories are presented to rule out or confirm ethylene glycol exposure. Another concern with laboratory support in ethylene glycol poisoning is correct identification of ethylene glycol because analysis of this substance is often problematic. In one case laboratories incorrectly identified an organic acid from an inherited metabolic disease as ethylene glycol, and in another case the intentional ethylene glycol poisoning of an infant was determined to be the results of an endogenous organic acid. The most robust analytical methods for determining ethylene glycol and glycolic acid are chromatographic methods. Ideally, screening methods for ethylene glycol should be confirmed by another method based on a different principle of analysis or include simultaneous metabolite analysis (glycolic acid). In centers where several ethylene glycol cases present annually, toxicology laboratories supporting these centers should incorporate glycolic acid monitoring in their ethylene glycol screening programs and include analysis of both ethylene glycol and glycolic acid during treatment (hemodialysis) in all confirmed poisonings. Measurement of glycolic acid provides important diagnostic and prognostic information that one cannot correlate with the amount of ethylene glycol in serum or whole blood.