ABSTRACTChildren with spastic diplegia as a result of cerebral palsy (CP) or HIV encephalopathy have different pathogenesis but present with similar motor deficits. Anti-retroviral therapy has allowed HIV-infected children to survive for longer but with this comes an increase in co-morbid complications that are not life-threatening but have an adverse effect on activity and participation. The aim of this study was to determine if there are similarities or differences with regards to function, tone and strength between children with spastic diplegia as a result of CP and those with spastic diplegia as a result of HIV encephalopathy. Participants with spastic diplegia (GMFCS I to IV) between the ages of 4 and 16 years were selected at four institutions in Johannesburg. Thirty-three HIV-infected children with spastic diplegia and 31 HIV-uninfected participants with CP spastic diplegia were assessed using the Gross Motor Function Measure 66 (GMFM-66), Functional Mobility Scale (FMS), Modified Ashworth Scale (MAS) for tone, and a hand-held dynamometer for strength. There were no statistically significant differences between the two groups with respect to function, strength and tone. When the groups were separated into ambulant (GMFCS I and II) and non-ambulant groups (GMFCS III and IV), there were no statistically significant differences between the two groups for GMFM (ambulant group p = 0.52, non-ambulant group p = 0.74), tone and strength. A minimally clinically important difference (MCID = 3.87) was found for the GMFM-66 in the ambulant group in favour of the HIV-infected participants. There was a trend for the HIV-infected ambulant participants to be weaker and have milder tone from proximal to distal. The non-ambulant HIV-infected participants tended to be stronger and have mild rather than severe tone from proximal to distal when compared to the CP group. Children with spastic diplegia as a result of HIV encephalopathy presented similarly to the HIV-uninfected children with spastic diplegic CP but tended to be more functional, have less severe tone and were weaker.