To determine the pharmacokinetics of a small lipophilic molecule in vivo, the distribution and accumulation of 99mTc-radiolabelled disofenin (diisopropylacetanilide iminodiacetic acid) were traced during 1991–1992 by scintigraphy and gamma well counting in winter flounder (Pleuronectes americanus collected from Boston Harbor and Long Island Sound in 1992), lobsters (Homarus americanus collected from Massachusetts Bay in 1991), and soft-shell clams (Mya arenaria purchased in 1991). The agent was distributed throughout the bodies of lobsters within 12 s, throughout flounder within 40 s, and throughout clams within 2 min. It was concentrated most strongly by the liver of flounder, which contained 61.2±7.8% of the injected dose within 1 h of injection, and by the lobster hepatopancreas. Accumulation also occurred in the flounder kidney, lobster antennal glands, and the kidney and pericardial glands of clams. The compound was rapidly excreted from the flounder liver into the gall bladder, and from the lobster hepatopancreas into the stomach. The data suggest its excretion from the lobster antennal glands and clam kidneys. The rate of clearance of disofenin from the body varied among species: 99±2.1% of the initial dose remained in flounder sampled 16 to 24 h after injection, compared to 80.5±7% remaining in the lobster after 15 h, and 87.4±5.9% remaining in clams after 27 h. The clearance rates in flounder and lobster are considered to be minimum values because of the lack of gut activity in unfed individuals. Overall, these in vivo tracer studies establish the utility of scintigraphy for assessing the uptake and excretion of a lipid soluble compound in different taxa, and may be applicable for evaluating disease and/or environmental effects on organ function in marine animals.