The measurement of ammonia, now known to be a normal constituent of all body fluids, is fraught with problems. An elevated ammonia level in blood (100 micromol/L or higher) is an indicator of an abnormality in nitrogen homeostasis. The collection, handling, storage, and analysis of blood samples, their limitations, and potential sources of error are discussed. New techniques that permit continuous or real-time estimates of systemic ammonia levels over a broad range are also discussed. The aim should always be to minimize the release of ammonia from the collected sample before analysis. Recommendations are made on the collection and processing of blood samples, for it is by standardization and rigid adherence to these techniques that the reliability of the test results will be improved.