open( IN, "big.file" ) or die $!;
while ( read( IN, my $cleartxt, 8192 ) > 0 ) {
    my $cryptxt = "";
    while ( $cleartxt ) {
        $tocrypt = substr( $cleartxt, 0, 16 );
        $cleartxt = substr( $cleartxt, 16 );
        if ( length( $tocrypt ) != 16 ) {
            $tocrypt .= " " x ( 16 - length( $tocrypt ));
        }

        # do what you need with Twofish to encrypt, and 
        # append result to $cryptxt
    }
    print $cryptxt;
}