1. ô-Aminolaevulinic acid (ALA) was determined by g.l.c. with electron-capture detection. Normal plasma level was 92 nmol/l (sd = 39, n = 89, range 24–270 nmol/l).
2. ALA was undetectable in 35 of 53 samples of normal cerebrospinal fluid (limit of assay 2 nmol/l). The mean of the other 18 samples was 19 nmol/l (sd = 10, range 6–36 nmol/l).
3. Salivary ALA was generally only 10–30% of the plasma level in normal and porphyric subjects.
4. Erythrocytes of normal and porphyric subjects contained no detectable ALA and were impermeable to its entry.
5. ALA clearance correlated closely with that of creatinine, consistent with it being excreted by glomerular filtration with limited tubular reabsorption.
6. In chronic renal failure, serum ALA was elevated to a maximum of three to four times the normal, but its urinary excretion was reduced, in keeping with lessened production.
7. In two cases of acute intermittent porphyria with overwhelming neuropathy the maximum plasma levels of ALA were 9 and 12 μmol/l. Haematin infusion decreased the ALA levels but without obvious clinical benefit. Limited neurological recovery occurred without major reduction in plasma levels of ALA.
8. One subject's attack was precipitated by pregnancy. The neonate was apparently normal, despite high levels of ALA in maternal plasma throughout gestation and a high level of ALA in the cord blood.
9. The observations described here do not support the view that ALA may be directly neurotoxic.