Contrast-enhanced MRI has been used previously to demonstrate BBB dysfunction during stage-2 infections . In the present study these findings have been confirmed and extended to examine earlier time-points following infection. It is now clear that barrier impairment becomes apparent during the haemolymphatic stage of the infection since a significant enhancement in signal intensity, to a mean of 15.85%, was apparent on day 14 post-infection compared to uninfected animals and those examined at the earlier time-point. The degree of barrier damage was further augmented to 25.41% at 21 days -post-infection and 28.82% on day 28 post-infection indicating that the trypanosome infection results in a progressive loss of BBB function. Although the increased signal intensity was most marked in the ventricular regions, infiltration of the contrast agent was not confined to these areas (Fig. 5) but found throughout the brain slice. Since signal enhancement was present throughout the brain parenchyma it is unlikely that the influx of contrast agent is restricted to traversal of the blood-CSF barrier and seems also to occur through the BBB. In earlier studies using an in situ perfusion model, the authors found evidence of BBB impairment, assessed by measuring [14C]sucrose concentrations in the parenchyma, during the late-stage of infection in a BALB/c mouse model , . Philip et al.  also found evidence of BBB dysfunction in a rat model of HAT. In this case rhodamine dye was injected into the jugular vein at specific time-points following infection. Low levels of dye leakage into the brain, at first confined to the thalamus and hypothalamus, were seen at 21 days post-infection with widespread penetration of both the white and grey matter evident by day 40 after infection. Again, this study fails to identify any barrier impairment at the earlier time-points after infection. The disparity between the current study and those previously published is likely a result of the differing methodologies used. MRI uses contemporary contrast agents that result in low levels of signal enhancement in the brain even in normal animals whereas rhodamine may remain excluded until more overt changes in barrier function develop. A similar situation exists with the use of sucrose as a marker of BBB permeability since this compound is considered to be excluded from the brain parenchyma under normal conditions . Interestingly, BBB dysfunction, assessed using the CSF/serum quotient of albumin, were detected in 6% of patients presenting with stage-1 T.b.rhodesiense infections . This figure increased to 42% when the stage-2 cases were examined indicating the development of progressive BBB impairment with advancing disease.