This study describes the consequences of sustained exposure to the nonspecific beta adrenergic agonist isoproterenol on the activity of lipoprotein lipase (LPL) in tissues that are sites for a large portion of the intravascular hydrolysis of triacylglycerols. Chronic exposure to isoproterenol was accomplished by means of osmotic pump infusion during four consecutive days, and assessment of the activity of LPL was performed at the end of the treatment. Four days of ISO infusion resulted in a large decrease in LPL activity of parametrial white adipose tissue, which declined to half of that found in the untreated group. In contrast, brown adipose tissue LPL activity was greatly increased (approximately threefold) by ISO treatment. The beta agonist raised LPL activity in red vastus lateralis muscle by a factor of four over control values, whereas heart enzyme activity was not significantly altered by the drug. These results demonstrate that catecholamines are part of the factors which determine the tissue specificity of LPL regulation. The tissue-specific changes in enzyme activity in response to isoproterenol, which are in very good agreement with the known metabolic actions of catecholamines in adipose and skeletal muscle tissues, attest to the key role of the enzyme in the partitioning of lipid substrates in situations of increased sympathetic activity.