Manipulation of cortical excitability can be experimentally achieved by the application of transcranial random noise stimulation (tRNS). TRNS is a novel method of non-invasive electrical brain stimulation whereby a random electrical oscillation spectrum is applied over the cortex. A previous study recently reported that application of weak 10-min tRNS over primary motor cortex (M1) enhances corticospinal excitability both during and after stimulation in the healthy human brain. Here, blood oxygenation level dependent (BOLD) MRI was used to monitor modulations in human sensorimotor activity after the application of 4-min tRNS. Activation maps for a right hand index-thumb finger opposition task were obtained for nine subjects after sham and 1-mA tRNS in separate sessions. TRNS of the left-hemispheric sensorimotor cortex resulted in a decrease in the mean number of activated pixels by 17%, in the hand area. Our results indicate that tRNS applied with different durations and/or in combination with a task might result in different outcomes. Application of tRNS to the human cortex allows an unnoticeable and thus painless, selective, non-invasive and reversible activity change within the cortex, its main advantage being the direction insensitivity of the stimulation. TRNS also provides a qualitatively new way of producing and interfering with brain plasticity, although, further research is required to optimise stimulation parameters and efficacy.