This study sought to demonstrate that clinically untypable strains of Haemophilus influenzae are derivable from previously capsulated ones. Penicillin-induced forms were employed to explore in vivo and in vitro a possible mechanism of the reversible cycle vegetative to L-phase revertant. Normal H. influenzae type b (Rab), capsule-deficient strain ATCC 9333, and experimental L-phase and its revertants were used in this investigation. Capsular antigens, polyribose phosphate (PRP) content of each strain was assayed by orcinol and rocket immunoelectrophoretic methods. Intra- and inter-strain PRP differences were statistically analysed. Strain differences between in vivo and in vitro passaged extracts of strain 9333 and 9333 were significant (t-test P less than 0.01). There were also significant differences in vivo and in vitro between penicillin-treated, L-phase infected mouse isolates and penicillin-free, L-phase infected mouse isolates; and also between penicillin-treated, L-phase infected mouse isolates and revertant Rab infected mouse isolates (Mann-Whitney U-test P less than 0.02, P less than 0.01, respectively). These findings suggest that untypable isolates of H. influenzae are derivable from otherwise capsulated strains, depending on decapsulating factors in the microenvironment. Clinical implications of the findings are discussed.