In vivo studies were performed to evaluate maturational changes in PAH extraction (EPAH) in the rabbit and to determine whether accelerated maturation of this process could be achieved. Fifty-four animals were injected with penicillin before study at 10, 14, 21, or 28 days of life. Forty-eight rabbits served as saline-injected controls. PAH extraction in controls increased from 29.3 +/- 2.4% at 10 days of age to 35.9 +/- 3.3% at 14 days, 59.7 +/- 3.5% at 21 days, 71.6 +/- 1.9% at 28 days, and 72.7 +/- 2.3% at 35 days of life. Penicillin injection on the 3 days before study resulted in enhancement of EPAH on days 10 and 14 to 42.7 +/- 2.4% and 65.0 +/- 3.2% (P less than 0.005). On days 21 and 28 less stimulation was noted (68.7 +/- 2.3%; 76.0 +/- 4.1%). Preinjection on days 6--9 with study delayed to day 14 also led to augmentation (46.7 +/- 3.7% P less than 0.05) but less than that achieved after injection on days 10--13. These data suggest that EPAH stimulation may be transient, descreases as maturation is approached and is likely related to substrate availability.