Using a conditioned suppression task, we examined the minimal conditions to establish context conditioning as induced by unpredictability of an unconditioned stimulus (US). We investigated whether a biologically significant US is necessary to produce such context conditioning effects. In this between-subjects experiment, we manipulated the nature of the US and US-unpredictability. In the Paired condition, the conditioned stimulus (CS) was always followed by the US, whereas in the Unpaired condition, the CS and the US were presented explicitly unpaired, that is, the CS was never followed by the US. Half of the participants received an aversive, biologically significant human scream, and the other half received a more neutral, biologically non-significant sound as US. Results show more contextual suppression in the Unpaired condition than in the Paired condition. We conclude that in an expectancy-based conditioning task, US-unpredictability, but not a biologically potent US, is crucial to establish context conditioning.