Adenosine and its 'Ri'- and 'P'-site analogs, N6-phenylisopropyladenosine and 2'-deoxyadenosine, stimulate, like insulin, lipoprotein lipase (LPL) activity in adipose tissue, an effect which is suppressed by cycloheximide. However, adenosine and its analogs do not potentiate the effects of submaximal insulin concentrations. As addition of cyclic AMP phosphodiesterase inhibitors abolishes the LPL stimulatory effects of insulin, adenosine and its analogs, this study suggests that these LPL effects are mediated through common mechanisms which are likely a decrease in cyclic AMP and an increase in LPL biosynthesis.