1. After injection into the renal medulla of rats Escherichia coli 06 variants reverted rapidly in vivo in the absence of penicillin. These variants had previously been shown to be stable in vitro.
2. Variants failed to survive following intramedullary injection when animals were receiving penicillin.
3. Late reversion of variants also failed to occur in animals treated with penicillin for only 1 or 2 days.
4. Variants survived and reverted more readily when injected in the renal medulla, compared with liver and spleen. Classical bacteria injected into the kidney, liver, and spleen were recovered in approximately equal numbers.
5. The histologic response to nonreverting variants, medium not containing variants, and killed variants was similar and was characterized by a fibrotic reaction with moderate round cell infiltration.
6. In contrast, the histologic response to reverting variants and to classical E. coli was characterized by an intense, acute, polymorphonuclear leukocytosis typical of acute pyelonephritis.