The stimulation of the human spermatozoal fertilizing ability by dibutyryl 3',5'-CAMP (diCAMP) and theophylline in suspected fertile and subfertile semen samples was demonstrated with the zona-free hamster ova penetration test. The penetration rates for the untreated (control) fertile and subfertile samples were 30% and 17%, respectively. DiCAMP increased the penetration rates to 54% and 37% (with 5 mM diCAMP) and to 46% and 36% (with 10 mM diCAMP) in the fertile and subfertile samples, respectively; theophylline increased the penetration rates to 56% and 35% (with 10 mM theophylline) and to 49% and 42% (with 20 mM theophylline) in the fertile and subfertile samples, respectively. These results indicate that diCAMP and theophylline can affect the fertilizing ability of human spermatozoa in vitro.