Growth hormone (GH) is used by athletes like bodybuilders to increase muscle strength and weight gain. On the other hand, chronic hypersecretion of GH in active acromegaly may result in outwardly hypertrophied but functionally weaker muscles. As a model for studying long-term effects of GH on muscle strength, we analysed transgenic mice (TM) carrying rat phosphoenolpyruvate carboxykinase-bovine GH (PEPCKbGH) fusion genes, which are expressed in liver and kidney but not in skeletal muscle. Circulating GH levels in TM ranged between 0.5 and 3 mu g/ml, resulting in increased (p < 0.001) body weight (wt) as well as increased (p < 0.01) weights of forelimb and hindlimb muscles. However, muscle weight/body wt ratios of TM were 16-20% smaller than in controls (p < 0.05). Forelimb grip strength of hemizygous TM (16 males, 132 +/- 45 days old, body wt = 56.8 +/- 8.3 g; 32 females, 146 +/- 38 days old, body wt = 54.9 +/- 6.1 g) and non-transgenic controls (28 males, 127 +/- 47 days old, body wt = 40.5 +/- 2.9 g; 33 females, 126 +/- 47 days old, body wt = 32.1 +/- 3.6 g) was determined using an automated grip strength meter. Data were computed by analysis of variance, taking into account effects of group, sex and age. Least-squares means estimated for the grip strength (N) of male TM (1.91) and controls (1.92) were significantly (p < 0.05) greater than those of female TM (1.78) and controls (1.61). A si,gnificant difference between groups was only seen in females (p < 0.01). Least-squares means estimated for grip strength/body wt ratios (N/10 g) of male (0.34) and female TM (0.33) were 29% and 35% lower than those of male (0.48) and female controls (0.51), respectively (p < 0.001). In summary, long-term elevated GH levels in TM increased muscle weight less efficiently than body weight, and muscle strength did not increase proportionally with muscle weight.