Abstract Objective: To investigate the variation in T1 and T2 relaxation times of normal appearing white matter (NAWM) and lesions in multiple sclerosis (MS) throughout the brain. Background: The magnetic resonance imaging (MRI) sequence fast FLAIR (fluid attenuated inversion recovery) has demonstrated overall increased lesion detection when compared to conventional or fast spin echo (FSE) but fewer lesions in the posterior fossa and spinal cord. The reasons for this are unknown, but may be due to variations in the T1 and T2 relaxation times within NAWM and MS lesions. Method: Ten patients and 10 controls underwent MRI of the brain which involved FSE, fast FLAIR and the measurement of T1 and T2 relaxation times. Results: Of 151 lesions analysed (22 infra-tentorial, 129 supra-tentorial), eight were missed by the fast FLAIR sequence. T1 and T2 relaxation times in normal controls were longer in the infra-tentorial, than supra-tentorial, region. Patient NAWM relaxation times were prolonged compared with control values in both regions. Lesions demonstrated longer relaxation times than either control white matter or patient NAWM in both regions, however this difference was less marked infra-tentorially. The eight posterior fossa lesions not visible on the fast FLAIR sequence were characterised by short T1 and T2 relaxation times which overlapped with the patient NAWM for both T1 and T2 and with control values for T2 relaxation times. Conclusion: Both lesion and NAWM relaxation time characteristics vary throughout the brain. The T1 and T2 relaxation times of infra-tentorial lesions are closer to the relaxation times of local NAWM than supra-tentorial lesions, resulting in reduced contrast between posterior fossa lesions and the background NAWM. Consequently the characteristics of some lesions overlap with those of NAWM resulting in reduced conspicuity. By utilising this information, it may be possible to optimise fast FLAIR sequences to improve infra-tentorial lesion detection.