The purpose of this work was to determine the relationship between lipoprotein lipase (LPL) activity and LPL mRNA in muscle and adipose tissue in fed and fasted rats. In control animals, the correlation between enzyme activity and LPL mRNA for adipose tissue, heart, soleus, fast red vastus lateralis, and fast white vastus lateralis muscle was r = +0.97. Twenty-four hours of fasting increased LPL activity 38% in heart, reduced it 59% in adipose tissue, and had no effect on activity in the three skeletal muscles analyzed. At the same time, relative LPL mRNA concentrations were reduced 25% in adipose tissue and elevated in heart, soleus, red vastus, and white vastus muscles when compared with control concentrations. Prolonging the fast to 6 days was accompanied by a 64% reduction in adipose tissue LPL activity and an increase in the activities of slow-twitch soleus (83%) and fast-twitch red vastus lateralis muscles (193%), with no enzyme activity change in heart or white vastus lateralis muscle compared with values obtained from control fed animals. LPL mRNA concentration was reduced 66% in adipose tissue, increased more than twofold in heart, soleus, and white vastus muscle, and increased threefold in red vastus muscle. Changes in relative LPL mRNA concentration in adipose tissue induced by fasting could, in part, be accounted for by the increases seen in total RNA concentration. The relationships between enzyme activity and LPL mRNA in muscle and adipose tissue were r = 0.97 and 0.77 for 1-day and 6-day fasted animals, respectively. These data indicate that LPL activity and mRNA expression are closely correlated over a variety of rat tissues from control fed rats. In addition, the tissue-specific changes in enzyme activity induced by prolonged fasting could, in part, be mediated through pretranslational control.